Steric and electronic effects on the oxidation of ortho-substituted benzhydrols by chromic acid

Tetrahedron.

Vol. 29, P&I 148 1 to 1486.

Pefgmm

Press

1973

Pnnted

m Great Bntam

STERIC AND ELECTRONIC EFFECTS ON THE OXIDATION OF ORTHO-SUBSTITUTED BENZHYDROLS BY CHROMIC ACID D. G. LEE* and M. RAPTIS Department of Chemistry, The University of Saskatchewan, Regina Campus, Regina, Canada S4S OA2 (Received WIUSA 16 November 1972; Received in UK forpublication 25 January 1973) Abstract-A study has been made of the oxidation of a number of substituted benzhydrols by chromic acid in aqueous acetic acid. The reaction rate constants are linearly proportional to the KR+values of the alcohols. ortho-Substitution increases the rate of reaction and reduces the magnitude of the primary kinetic isotope effect. The major result of steric crowding appears to be an increase in the energy of the reactants, while the main electronic effect of substituents is to stabilize or destabilize the transition

Chromium (VI) has been employed extensively as an agent for the oxidation of primary and secondary alcohols; it converts primary alcohols to aldehydes or carboxylic acids and secondary alcohols to the corresponding ketones.’ Because of its importance to synthetic organic chemistry a great deal of work has been done in an attempt to elucidate the mechanism of its reactions, and it would seem that the main characteristics have been well defined.2*3 The electron transfer step has been shown to be preceded by a number of equilibria, some of which involve the formation of chromate esters as indicated below.1*4*5 Cr,OF + Hz0 e +HCrO,+H HCrOh + 2H+ + A- = HCrOh + ROH w H&r%& + ROH e H,CrO,A + ROH e

2HCr0, H,CrO HC& + H,O RO-CrO,+ Hz0 ROCrQH + He0 ROCrO,A + H,O

The esters formed in these equilibria then undergo decomposition accompanied by electron transfer and C-H bond cleavage. Although it is known from the effect of deuterium substitution on the rates of reaction that this step is usually ratedetermining,4 the exact mode of decomposition has not been defined. Westheimep originally suggested that the esters would decompose by transfer of a proton to a base such as water in the rate determining step (Eq 1). R YO%rOsH R’ % H,O

-

R\ R’

C=O + HCrOs- -I-H,O+

However other workers have suggested that the a-hydrogen is transferred internally to a neighbouring oxygen as depicted below.6-10 The strengths and weaknesses of these various suggestions have been thoroughly discussed elsewhere.1*2

The ester mechanism has been tried and tested in a variety of ways” but it would appear that at the present time there is little doubt as to its validity. Firm evidence for ester formation was obtained from a kinetic study of the oxidation of a sterically hindered alcohol, 3/3-28diacetoxy-6P-hydroxy18/3-12-oleanene.‘2 The rate of oxidation of this alcohol was found to be unchanged by deuterium substitution in the a-position suggesting that the ester forming step had become rate determining. Furthermore, the spectroscopic observation of an intermediate ester has been reported.13*14 In addition results which seem to indicate a steric rate retardation arising from angle strain in the developing carbonyl have been published.15 Both substituent and steric effects on the rate of reaction have been extensively studied and although these effects could change the magnitude of both the equilibrium constants for ester formation and the rate constant for the electron transfer step, evidence indicates that the primary effect is on the latter.8 It appears clear that the effect of electron donating and electron withdrawing substituents is to stabilize or destabilize an electron deficient transition state; however, the reasons for steric acceleration are not as obvious and various explanations have been offered.‘0*‘6

1481

1482

D. G. LEE and M. RAFTIS

Since most of the previous work on steric effects has been done using cyclic and bicyclic alcohols as reductants, we have attempted to obtain new evidence by measuring the rates of oxidation of a group of ortho-substituted benzhydrols. EXPERIMENTAL Preparation of substrtuted benzhydrols. The substituted benzhydrols used in this study were prepared by three standard procedures that have been previously described in the literature: (i) reduction of the corresponding ketone with LAH or deutende,” (ii) reaction of an arylmagnesium halide with an aromatic aldehyde,i8 and (iii) reaction of an a&magnesium halide with methyl formate I9 The reactions have been sumor methyl formate-& marized in Table 1. In everv case the IR and NMR snectra were consistent with the assumed structure of the products. Kinetic method. The rates of these reactions were studied in a solvent consisting of 69.0% acetic acid, 17.7% water and 13.3% HzS04 (by weight). Because the reactions are very rapid under these conditions it was convenient to use stopped-flow techniques. The instrument employed was a Dun-urn Model D-110 Stopped-Flow Spectrophotometer equipped with a thermostated cell compartment. In a typical experiment solns of KQO, (1.25 x 10-4M) and benzhydrol (7.50 x 10mSM) were prepared in the AcOH-water-HZSO1 solvent, and degassed by freezing and then slowly thawing the soln under reduced pressure (70 mm). The solns were then rapidly mixed using the instrument and plots of transmittance vs time were recorded on the oscilloscope. Then plots of In (absorbance-final absorbance) against time were prepared and the pseudo-first order rate constants calculated. A typical plot has been reproduced in Fig. 1. -I

pKa+ values had previously been measured for all but four of the alcohols required for this study, and using the HR function it was possible to calculate these constants for the remaining benzhydrols (2-methylbenzhydrol, 2,4,4’,6-tetramethylbenzhydrol, 2,2’,4,4’-tetramethylbenzhvdrol and 2.2’.4.4’.6-oentamethvlbenzhvdrol) bv measuring the ratios of [R+]i[ROH] at different sulfuric acid concentration in the following manner. The A,,,., and approximate extinction coefficient were first defined for each diphenylcarbonium ion by dissolving a known quantity in 98% HzS04 and recording the spectrum of the carbonium ion. Next a solution containing an appropriate concentration of the benzhydrol was prepared by dissolving a weighed amount of the alcohol in methanol. Portions of this solution (O-03 ml) were transfered to 3-Oml volumetric flasks using a microliter syringe fitted with a Chaney adapter, the flasks were filled to the mark with H,SO, solns of different concentrations and the absorbance of each soln was measured at the previously determined A,,. Plots of absorbance against Ha gave typical titration curves for each of the alcohols. (Fig 2).

-

Fig. 2. Titration curves for the ionization of benzhydrols: (0) 2,2’,4,4’-Tetramethylbenzhydrol, (Cl) 2,2’,4,4’-6Pentamethylbenzhydrol, (m) 2,4,4’,6-Tetramethylbenhydrol, and (0) 2-Methylbenzhydrol. Tlmc.

MC

Fig. 1. Typical pseudo-first-order

rate plot.

pK,+ Measurements When dissolved in cone H,SO, solns diphenyl-carbinols form carbonium ions according to Eq 2. R++HzO

_X

ROH+ H+

121

From these titration curves values of log [R+I/[ROHl were calculated and plotted against HR (Fig 3). From the intercepts of these linear plots it was then possible to calculate the corresponding p&+ values. The complete results obtained from such an analysis of our results and those reported by Deno et aP”.*’ have been summarized in Table 2. RESULTS AND DISCUSSION first order rate constants obtained in this study have been summarized in Table 3. From The pseudo

The I(R+ values for these compounds may be obtained this data it is readily apparent that substituents in by use of the acidity function developed by Deno et ~l.~“*~’ the para positions exert the expected electronic This function, originally designated by Co, but more effect and that increasing Me substitution in the recently as Hk, is defined by Eq 3. ortho positions of benzhydrol increases the rate of Ha = pKa+ -log [R+]/[ROH] 131 oxidation. Although it is practically impossible to

Benzophenone + LiAlH, Benzophenone + LiAlD, 4-Methylbenzophenone + LiAlH, 4,4’-Dimethylbenzophenone + LiilH, CChlorobenzophenone + LiAlH, Commercially available 2-Methylphenyl magnesium bromide + benzaldehyde 4-Methylphenyhnagnesium bromide + 2,4,6-trimethylbenzaldehyde 2,4-Dimethylphenyhnagnesium bromide + 2,4,6-trimethylbenzaLdehyde 2.4,6-Trimethylphenyhnagnesium bromide + 2,4,6-trimethylbenzaldehyde 2-Methylphenylmagnesium bromide + methyl formate 2,4-Dimethylphenyhnagnesium bromide + methyl formate 2,4,6Trimethylphenylagnesium bromide + methyl formate-u-d

Reactants

98-99” (101°)34d

90

151-152

124-124.5” (119-119~5°)30e

50

45

153154” (1506-151.40)”

106- 107%

52 70

103- 104”

67-68” (69”)“” 66-67’ 54-55” (52”)ti 72-73” (71-72”)50c 62-63” (59-61”)= 945-95” (8!ww)3Z 935-94.5” (95”)“M

Melting Point”

11

52

5; 73

46 53

Yield (%)

aLiterature values in parenthesis *No literature values available. Elemental analysis: Cak., C-84.95%, H-&38%; found C-8560%, H-8.55% cNo literature values available. Elemental analysis: Calc., C-84*%, H-8.71; found C-84*70%, H-8.91% dElemental analysis: Cak., C-84-95%, H-8.33%; found C-84*53%, H-8.2%.

2,2’,4,4’ ,6,6’-Hexamethylbenzhydrol-a-d

2,2’,4,4’-Tetramethylbenzhydrol

2,2’-Dimethylbenzhydrol

2,2’ ,4,4’ ,6,6’-Hexamethylbenzhydrol

2,2’,4,4’,6Pentamethylbenzhydrol

2,4,4’,6Tetramethylbenzhydrol

Benzhydrol Benzhydrol-a-d CMethylbenzhydrol 4,4’-Dimethylbenzhydrol CChlorobenzhydrol 4,4’- Dichlorobenzhydrol 2-Methylbenzhydrol

Benzhydrol

Table 1. Preparation of substituted benzhydrols

1484

D. G.

LEE and M. ms Table 3. Pseudo first order rate constants for oxidation of substituted benzhydrols by Chromium(W) in 69.0% acetic acid, 17.7% water and 13.3% H$O,, [alcohol] = 3.75 X 10e9M,[Cr”q = 1.25 X lO+M, Temp. = 40.0 +-O-1”.

Compound

k,(sec.+)’

4-Chlorobenzbydrcl 08978 & 08003 4,4’-Dichlorobenzhydrol O-0855-c 0.0011 Benzhydrol 0*102*0*001 4-Metbylbenzhydrol 0~172~OGOl 4,4’-Dimetbylbenzbydrol 0.251 f 0*002 2-Metbylbenzbydrol 0*117+0801 2,2’-Dimetbylbenzbydrol 0*148~0~003 2,4,4’,6-Tetmmetbylbenzhydrol 0.255 Z!Z 0.003 I I 1 I 2.2’,4,4’-Tetrametbylbenzbydrol 0.357 f 0806 -10 -12 -14 -8 2.2’.4,4’.6-Pentametbylbenzbydrol 0.539 + 0807 HR 2,2’,4,4’,6,6’-Hexamethylbenzbydrol 0.794 + 0.011 Benzhydrol-a-d 0.0258 f 0*0002 Fig. 3. Plots for pKs+ determinations of 2,2’,4,4’,dPen2,2’,4,4’,6,6’-Hexamethylbenzbydrol-a-d 0.247 & 0.002 2,2’,4,4’-Tetramethylbenzbydrol, tamethylbenzbydrol, 2,4.4’,6-Tetrametbylbenzhydrol, and2-Metbylbenzhydrol (left to right). The average rate constant from four or more determinations. Errcr indicated as (A) is the probable deviation from differentiate between the polar and the steric the mean. effects of ortho substituents it is significant to cation that the main effect of substituents is to note that a good correlation exists between log k, stabilize the developing carhonyl, although the low and pKa+ values (Fig 4). Hence although the effect slope of Fig 5 suggests again that the sp2 character is not as great, it would appear that ortho substituof the transition state is far from fully developed. ents inlluence the rates of oxidation in much the Further information concerning the nature of the same way as they do the formation of carbonium transition state comes from a consideration of the ions. The low slope of the plot in Fig 4 is in accord primary deuterium isotope effects. Theory prewith the suggestion previously made that the transition state of the reaction has more sp3 than sp2 dicts that the magnitude of the isotope effect is related to the symmetry of the transition state, with character.22 the largest effects being observed for the most It is well known that electron donating substitsymmetrical situation.% A small isotope effect uents increase the rate of reactiona~23*24presumwould be consistent with a transition state in which ably through stabilization of the transition state bond was either extensively cleaved which has developed some sp2 character. This is the A-H or one in which it was relatively intact, but not illustrated in Fig 5 where the rate constants for the with one in which the a-hydrogen is in a symmetrioxidation of several substituted c+phenylethanolP cal position with respect to the oxidant and the have been plotted against the CO stretching frereductant; i.e., assuming that the hydrogen is transquencies of the corresponding ketonesz5. A correlaferred from the a-carbon atom to an 0 atom, a tion between rate and carbonyl stability is an indiI

Table 2. pKs+ values for substituted benzhydrols Substituents

pK,+

4,4’-Dichloro 4Chloro Unsubstituted Unsubstituted 2-Methyl 2,2’-Dimetbyl CMetbyl 2,4,4’,6_Tetramethyl 4,4’-Dimetbyl 2,2’,4,4’-Tetrametbyl 2,2’,4,4’.CPentamethyl 2.2’.4,4’,6,6’-Hexametbyl

- 1397 - 13.7 - 13.36 - 13.71 - 13.05 - 12.43 -11.6 - 11.37 - 10.38 - 9.88 - 9.65 -6.58

ma

n*

Ie

1.08 5 0.997 (No data avail.) 1.16 4 0999 097 5 0987 0.98 8 0.980 094 5 0998 (No data avail.) 084 10 0994 0.89 4 0999 0.83 9 0997 0.80 9 0.995 0.88 6 0999

‘Slope of the plot of log [R+]/[ROHl against -HR bNumber of points Correlation coefficient

Reference Ref. X20 Ref. X21 Ref. AC20 This work This work Ref. X20 Ref. #21 This work Ref. X20 This work This work Ref. #20

1485

Effects on the oxidation of o&o-substituted benxhydrols

that the force constant for the O-H bond is greater than that for the C-H bond. Such a conclusion is certainly consistent with the known absorption frequencies of C-H and O-H bonds in stable compounds. Consequently it would appear that the a-carbon remains primarily spa even though the C-H is extensively cleaved in the transition state. Turning to a consideration of steric effects it has been observed in a wide variety of systems that increases in steric hindrance also increases the rate of oxidation.27*2* However, the rate increases cannot be attributed to the same kind-of transition state stabilization that electronic effects produce; there is no correlation between reaction rates and carbonyl stretching frequencies for sterically hindered alcohols.1o For example, the rate of oxidation of endo-5,6-trimethylene-endo-2-norbomanol

-02-

A? 0 -0

-06-

II 14

I

I

II

6

-P&T

Fig. 4. Plot of log k, v. - PKa+. Slope = O-14,Correlation coefficient = 0.97.

large isotope effect will be observed only if the partial bond between the C-H is approximately equal in strength to the partial bond between the H-O in the transition state. Conversely, a small isotope effect will be observed only if the strengths of the partial C-H and O-H bonds are very unequal in the transition state. All available data (Table 4) indicate that the isotope effect for this reaction is smaller for alcohols containing substituents which increase the sp* character of the transition states, thus suggesting that the greater a symmetry introduced by these substituents is related to a more extensive cleavage of the carbon-hydrogen bond. Consequently we are drawn to the conclusion that although the (rcarbon atom remains largely sp3 in character in the transition state the C-H bond is extensively cleaved. While this may seem on the surface to be a contradiction it may simply reflect the possibility

2

H

-039-

-071-

1

1

1667

I

1692 Y.

1697 cm-’

Fig. 5. Plot of log k2 for the oxidation of substituted aphenylethanols” v. vc_u for the corresponding acetophenones 5. Slope = 6.6 X lo-’ cm. Correlation coefficient = 099.

Table 4. Effect of substituents on primary deuterium isotope effects Alcohol

Substituents

Conditions

(a) a-PhenylethanoPO

phfethoxy pchloro

30% AcOH. 0.250 H+ 30% AcOH, 0.250 M H+

(b) Phenyltri8uoromethylcarbiil*

p-Methyl none m-Bromo m-Nitro 3.5Dinitro

72.2% AcOH. 72.2% AcOH. 72.2% AcOH. 72.2% AcOH, 72*2%AcOH,

(c) 2-PropanoP

None l,l,l-Tritluoro

50.1% H,SO, 50.l%H$O,

3.2 M HCIO, 3.2 M HCIO, 3.2 M HClO, 3.2 M HClO, 3.2 M HCIO,

kJka ;:: 7.4 85 9.8 12.2 12.9 6.3 10.5

1486

D. G. LEE and M. RAPTIS Table 5. Steric effects on the primary deuterium isotope effects Alcohol

Substituents

Conditions

ka/ka

(a) endo-NorbomeoPr

exe-Benzo endo-Benzo exe-Naphtha endo-Naphtha

70% AcOH, 70% AcOH, 70% AcOH, 70% AcOH,

(b) Benzhydrol

None 2,2’,4,4’,6,6’-hexamethyl

69% AcOH, 13.3% H,SO, 69% AcOH, 13.3% H&SO,

0.1 0.1 0.1 0.1

M M M M

HClO., HClO, HClO, HCIO,

“The authors report k,/k, = 5.85 for this compound. However a recalculation rate data indicates a value of 6.2. is 15 1 times greater than that of en&-5,dtrimethylene-exo-2-norbomanol despite the fact that they both give the same product.2BConsequently in these cases the rate accelerating effects must be due to an increase in the energy of the reacting alcohols rather than to stabilization of the transition state. It is of interest to note that the isotope effects have also been observed to decrease with increased steric hindrance for all systems that have been studied (Table 5). These observations must also be as a consequence of changes in the reactants. Increasing the steric hindrance of the alcohols would reduce the H-C-Obond angles, increase the p-character of the c-C--H bond and decrease the force constants. This would lead to a reduction in the magnitude of the isotope effect as observed. Hence it would appear that the increases in rate (and decreases in isotope effect) caused by electron donating substituents and steric hindrance are not attributable to identical phenomena. Electron donating substituents increase the sp* character of the transition state whereas steric effects destabilize the reactant alcohols. Acknowfedgemenf-The authors are grateful to the National Research Council of Canada for financial support of this work.

6.2” 6.1 5.8 3.7 4.0 3.2 using the

9A. K. Awasthy, J. Rocek and R. M. Moriarty, J. Am. Chem. Sot. 89,540O (1967)

IoH. Kwart, Suomen Kemistilehti A34, 173, (1961) ‘?I Rocek and J. Krupicka, Cull. Czech. Chem. Comm. &, 2068 (1958)

‘*J. Rocek, F. H. Westheimer, A. Eschenmoser, L. Moldovanyi and J. Schreiber, Helv. Chim. Acta 45, 2554 (1962)

r3K. B. Wiberg and H. Schafer, J. Am. Chem. Sot. 89,455 (1967) 91,927 (1969) 14D. G. Lee and R. Stewart, J. Ora. Chem. 32, 2868 (1967) 15P.Muller, Helv. Chim. Acta 53,1869 (1970) ‘6E. L. Eliel. S. H. Schroeter. T. J. Brett. F. J. Biros and J. C. Richer, J. Am. Chem. Sot. 88,3327(1966) “I-I. 0. House, Modern Synthetic Reactions pp. 24-32. Beniamin, New York, (1965) l*M. S. Kharasch and d. Rei&uth, Grignard Reactions of Nonmgtallic Substances pp. 138-528. Prentice-Hall, (1954) rsR. C. Fuson and H. L. Jackson, J. Am. Chem. Sot. 72, 351(1950) *ON. C. Deno, J. J. Jaruzelski and A. Schreisheim, Ibid., 77,3044 (1955) 21N. C. Deno and A. Schreisheim, Ibid., 77,305 l(l958) 22c. F. Wdcox. M. Sexton and M. F. Wilcox. J. Org.

Chem 28,1079 (1963) 23H. Kwart and P. S. Francis, J. Am. Chem. Sot. 77,4907 (1955)

**D. G. Lee, W. L. Downey and R. M. Maass, Canad. J. Chem. 46,441(1968) 25R. N. Jones, W. F. Forbes and W. A. Mueller, Ibid., 35, 504 (1957)

REFERENCES ‘K. B. Wiberg, in Oxtdation in Organic Chemtstry (Edited by K. B. Wiberg), Part A, pp. 69-184. Academic Press, New York, N.Y. (1956) 2R. Stewart, Oxidation Mechanisms, pp. 33-76. W. Benjamin, New York (1964) 3D. G. Lee, Oxidation: Technrques and Applications in Organrc Synthesis (Edited by R. L. Augustine) pp. 5663. Marcel Dekker, New York, N.Y. (1969) 4F. H. Westheimer, Chem. Rev. 45,419 (1949) SD. G Lee and R. Stewart, J. Am Chem. Sot. 86,305l (1964) BR. Stewart and D. G. Lee, Canad. J. Chem. 42, 439 (1964) ‘I-I. Kwart and P. S. Francis, J Am. Chem. Sot. 81,2 116

(1959) BR.M. Lanes and D. G. Lee. J. Chem. Ed. 45,269 (1968)

*OF.H. Westheimer, Chem. Rev. 61,265 (1961) *7R. Baker and T. J. Mason, J. Chem. Sot (B) 988 (197 1) 28E. L. Eliel, N. L. Allinger, S. J. Angyal and G. A. Morrison, Conformation Analysis pp. 81-83 and 271-273. Wiley, New York, (1965) “I. Rothberg and R. V. Russo, J. Org. Chem. 32,2003 (1967) 30Dtcttonary

of Organic Compounds, (Edited by J. R. A. Pollock and R. Stevens) (a) p. 1286, (b) p. 2731, (c) p. 13 12, (d) p. 2731. Eyre and Spottiswoode, London (1965) 31W. E. Bachmann, E. Carlson and J. C. Moran, J. Org. Chem. 13,916, (1948) 3W. D. Cohen, Res. Trav. Chum. 38,114 (1919) “H. A. Smrth and B. B. Stewart, J. Am. Chem. Sot. 79, 3693 (1957)

34J. Coops, W. T. Nanta, M. J. E. Emsting and A. C. Farber, Rec. trav. Chem 59.1109 (1940)